Breast Cancer Risk Pathways
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ABSTRACT:
PROVIDER: PRJNA306393 | ENA |
REPOSITORIES: ENA
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Project description:Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from 8 women provided 5 paired-groups (cancer versus control) for analysis of differentially expressed proteins: 2 within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and 3 across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the 5 comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research.
2017-12-18 | PXD007066 | Pride
Project description:Worldwide an ever-increasing number of women are prescribed estrogen modulating therapies (EMTs) for the treatment of breast cancer. In parallel, aging of the global population of women will contribute to risk of both breast cancer and Alzheimer’s disease. To address the impact of anti-estrogen therapies on risk of Alzheimer’s and neural function, we conducted medical informatic and molecular pharmacology analyses to determine the impact of EMTs on risk of Alzheimer’s followed by determination of EMT estrogenic mechanisms of action in neurons. In a propensity matched data set of 260,232 women with breast cancer, medical informatic analyses indicated that EMTs were associated with reduced risk of AD which was driven by patients receiving tamoxifen or aromatase inhibitors whereas raloxifene was ineffective independently validating earlier reports. Mechanistically, a comparative analysis of EMTs vs estradiol was conducted to determine whether EMTs exerted estrogenic action in neural cells in-vitro and in brain in-vivo. Outcomes of mechanistic analyses indicated that select EMTs induced estrogenic action and pathways in neural cells including promoting neuronal morphological plasticity, electrophysiological indicators of synaptic connectivity, mitochondrial number and function and induction of transcriptomic pathways consistent with estrogenic outcomes. Collectively, these data provide both clinical and mechanistic data indicating that select EMTs exert estrogenic agonist action in neural tissue that are associated with reduced risk of Alzheimer’s disease while simultaneously acting as effective estrogen receptor antagonists in breast.
2023-11-01 | GSE241054 | GEO
Project description:<p>We sought to identify genomic variants that differed between individuals who developed familial breast cancer and individuals who had a family history of breast cancer but who had not developed breast cancer. We aggregated these data at the pathway level to identify pathways that play a role in familial breast cancer development. We profiled peripheral blood cells, extracted DNA, and sequenced the DNA using exome-capture sequencing to identify genomic variants in these samples. For 34 of the 35 samples, we also profiled peripheral blood using Affymetrix Human Exon 1.0 ST Array microarrays. Those data can be found in Gene Expression Omnibus under accession identifier GSE47862.</p>
| phs001044 | dbGaP
Project description:Breast cancer develops through the accumulation of genomic changes in the ductal epithelia cells of normal breast tissue. A determination of whether gene expression changes in ductal cells is associated with an increased risk for breast cancer is needed. We sought to determine if the global gene expression profiles of ductal cells of women at high risk for breast cancer or with cytologic ductal epithelial atypia differed from those of women at normal risk or without cytologic atypia. We used microarrays to detail the gene expression profile of breast ductal cells associated with normal risk or high risk for sporadic breast cancer and with or without cytologic epithelial atypia. We did not identify any separation of the sample groups (normal risk vs high-risk, or atypia vs nonatypia) according to expression of subgroups of genes.
2020-07-05 | GSE153796 | GEO
Project description:We report the application of FAIRE seq in Human Mammary Epithelial Cells for identifying the breast cancer risk functional SNPs in enhancer region. Examination of FAIRE assay in HMEC
2013-05-10 | E-GEOD-46074 | biostudies-arrayexpress
Project description:Genome-wide association studies (GWASs) have identified thousands of single nucleotide polymorphisms (SNPs) associated with human traits and diseases. But because the vast majority of these SNPs are located in the noncoding regions of the genome their risk promoting mechanisms are elusive. Employing a new methodology combining cistromics, epigenomics and genotype imputation we annotate the noncoding regions of the genome in breast cancer cells and systematically identify the functional nature of SNPs associated with breast cancer risk. Our results demonstrate that breast cancer risk-associated SNPs are enriched in the cistromes of FOXA1 and ESR1 and the epigenome of H3K4me1 in a cancer and cell-type-specific manner. Furthermore, the majority of these risk-associated SNPs modulate the affinity of chromatin for FOXA1 at distal regulatory elements, which results in allele-specific gene expression, exemplified by the effect of the rs4784227 SNP on the TOX3 gene found within the 16q12.1 risk locus. Examination of histone modification H3K4me2 in untreated and E2 treated cells
2012-08-17 | E-GEOD-31151 | biostudies-arrayexpress
Project description:Dietary energy restriction (DER) reduces risk of spontaneous mammary cancer in rodents. In humans, DER in premenopausal years seems to reduce risk of postmenopausal breast cancer. Markers of DER are required to develop acceptable DER regimens for breast cancer prevention. We therefore examined markers of DER in the breast, adipose tissue, and serum. Nineteen overweight or obese women at moderately increased risk of breast cancer (lifetime risk, 1 in 6 to 1 in 3) ages between 35 and 45 were randomly allocated to DER [liquid diet, 3,656 kJ/d (864 kcal/d); n = 10] or asked to continue their normal eating patterns (n = 9) for one menstrual cycle. Biopsies of the breast and abdominal fat were taken before and after the intervention. RNA was extracted from whole tissues and breast epithelium (by laser capture microdissection) and hybridized to Affymetrix GeneChips. Longitudinal plasma and urine samples were collected before and after intervention, and metabolic profiles were generated using gas chromatography-mass spectrometry. DER was associated with significant reductions in weight [-7.0 (+/-2.3) kg] and in alterations of serum biomarkers of breast cancer risk (insulin, leptin, total and low-density lipoprotein cholesterol, and triglycerides). In both abdominal and breast tissues, as well as isolated breast epithelial cells, genes involved in glycolytic and lipid synthesis pathways (including stearoyl-CoA desaturase, fatty acid desaturase, and aldolase C) were significantly down-regulated. We conclude that reduced expressions of genes in the lipid metabolism and glycolytic pathways are detectable in breast tissue following DER, and these may represent targets for DER mimetics as effective chemoprophylactic agents Transcriptomic and Metabolomic intervention study of continuous energy restriction in 19 participants
2016-07-13 | GSE66159 | GEO
Project description:Human breast cancer tissue samples from 18 patients with high-risk or low-risk MammaPrint breast cancer were analyzed. The membrane fractions were enriched, and the extracted proteins were reduced, alkylated, digested with Lys-C and Trypsin, and labelled with iTRAQ4plex: 114; high risk; 115; low risk. Identification results were filtered at 1% false discovery rate (FDR) thresholds by searching against a randomized decoy database using Mascot at peptide and protein levels.
2016-10-17 | PXD005163 | JPOST Repository
Project description:We sought to identify circulating microRNAs (miRNAs) from blood plasma that could be used as biomarkers to detect breast cancer existing in high-risk benign breast tumors. Plasma samples were collected from patients with early-stage breast cancer (CA), high- (HB), moderate- (MB), and no-risk (Be) benign tumors. The miRNAs we have identified have the potential to develop into a crucial blood-based screening tool to help monitor the development of breast cancer in benign breast tumors.
2023-04-20 | GSE225117 | GEO
Project description:The underlying biology through which established breast cancer risk factors contribute to disease risk is not well characterized. One key risk factor for breast cancer is age, and age-related DNA methylation alterations may contribute to increased risk of disease. Here we assessed normal breast tissues and tested the relation of DNA methylation with known breast cancer risk factors. Cancer-free women donated breast tissue biopsy specimens through the Susan G. Komen Foundation and provided detailed risk factor data (n=100). Bisulfite modified DNA was profiled for DNA methylation genome-wide using the Infinium 450K DNA methylation array. We tested the relation of known breast cancer risk factors such as age, BMI, parity, and family history of disease with DNA methylation adjusted for variation in cell type proportions using a novel cellular mixture deconvolution algorithm. We identified 787 CpGs that exhibited significant (FDR adjusted, q-value < 0.01) differential DNA methylation associated with subject age, but not with other breast cancer risk factors. We observed an enrichment among the risk factor-related CpGs for Polycomb group target genes (Fisher’s Exact test, P = 1.74E-06), and breast myoepithelial cell enhancer regions (H3K4me1; Fisher’s Exact test, P = 7.1E-20). We validated our risk factor-related findings in two independent populations of normal breast tissue (n=18 and n=97). In addition, age-related CpGs were further deregulated in both pre-invasive (DCIS, n=40) and invasive breast cancers (TCGA, n=731). Overall, our results suggest that the breast cancer risk factor age contributes to epigenetic dysregulation in normal breast tissue that exhibit progressive changes in cancer.
2017-06-20 | GSE88883 | GEO